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While randomized controlled trials (RCTs) are critical for establishing the efficacy of new therapies, there are limitations regarding what comparisons can be made directly from trial data. RCTs are limited to a small number of comparator…

The interpretation of randomised clinical trial results is often complicated by intercurrent events. For instance, rescue medication is sometimes given to patients in response to worsening of their disease, either in addition to the…

Methodology · Statistics 2021-02-12 Hege Michiels , Cristina Sotto , An Vandebosch , Stijn Vansteelandt

Identifying the most powerful test in multiple hypothesis testing under strong family-wise error rate (FWER) control is a fundamental problem in statistical methodology. State-of-the-art approaches formulate this as a constrained…

Methodology · Statistics 2025-12-17 Prasanjit Dubey , Xiaoming Huo

In most nonrandomized observational studies, differences between treatment groups may arise not only due to the treatment but also because of the effect of confounders. Therefore, causal inference regarding the treatment effect is not as…

Methodology · Statistics 2018-07-04 Debashis Ghosh

Adaptive designs(AD) are a broad class of trial designs that allow preplanned modifications based on patient data providing improved efficiency and flexibility. However, a delay in observing the primary outcome variable can harm this added…

Methodology · Statistics 2025-09-26 Aritra Mukherjee , Michael J. Grayling , James M. S. Wason

Many statistical problems can be addressed by applying a multiple testing procedure (MTP) that controls either the Family-wise Error Rate (FWER) or False Discovery Rate (FDR) under unknown arbitrarily-interdependent $p$-values, without…

Methodology · Statistics 2026-05-21 George Karabatsos

In paired experiments, participants are grouped into pairs with similar characteristics, and one observation from each pair is randomly assigned to treatment. Because of both the pairing and the randomization, the treatment and control…

Applications · Statistics 2019-05-22 Edward Wu , Johann A. Gagnon-Bartsch

The win ratio offers a flexible approach to incorporate the hierarchy of clinical outcomes into the analysis of a composite endpoint, enabling simultaneous consideration of multiple outcome types, unlike traditional time-to-first-event…

Methodology · Statistics 2025-07-22 David Kronthaler , Matthias Schwenkglenks , Felix Beuschlein , Ulrike Held

Platform trials have become increasingly popular for drug development programs, attracting interest from statisticians, clinicians and regulatory agencies. Many statistical questions related to designing platform trials - such as the impact…

We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…

Applications · Statistics 2011-08-09 Ying Yuan , Guosheng Yin

Simultaneous statistical inference has been a cornerstone in the statistics methodology literature because of its fundamental theory and paramount applications. The mainstream multiple testing literature has traditionally considered two…

Statistics Theory · Mathematics 2025-03-21 Monitirtha Dey , Subir Kumar Bhandari

Leveraging external or historical data to improve the efficiency of randomized clinical trials without introducing bias or inflating the Type I error rate remains challenging. Recent work on externally trained prognostic scores, such as…

Methodology · Statistics 2026-05-28 Junyi Zhou , Qing Liu , May Mo , Amy Xia

A new approach to adaptive design of clinical trials is proposed in a general multiparameter exponential family setting, based on generalized likelihood ratio statistics and optimal sequential testing theory. These designs are easy to…

Statistics Theory · Mathematics 2011-05-25 Jay Bartroff , Tze Leung Lai

Response-adaptive randomisation (RAR) can considerably improve the chances of a successful treatment outcome for patients in a clinical trial by skewing the allocation probability towards better performing treatments as data accumulates.…

Applications · Statistics 2017-03-14 Sofia S. Villar , Jack Bowden , James Wason

Nonlinear longitudinal proportional effect models have been proposed to improve power and provide direct estimates of the proportional treatment effect in randomized clinical trials. These models assume a fixed proportional treatment effect…

Methodology · Statistics 2026-01-23 Michael C. Donohue , Philip S. Insel , Oliver Langford

Crossover designs are an extremely useful tool to investigators, whilst group sequential methods have proven highly proficient at improving the efficiency of parallel group trials. Yet, group sequential methods and crossover designs have…

Methodology · Statistics 2017-10-11 Michael Grayling , James Wason , Adrian Mander

Background: Stepped wedge cluster randomized trials (SW-CRTs) involve sequential measurements within clusters over time. Initially, all clusters start in the control condition before crossing over to the intervention on a staggered…

Methodology · Statistics 2026-01-21 Jale Basten , Katja Ickstadt , Nina Timmesfeld

Most comparisons of treatments or doses against a control are performed by the original Dunnett single step procedure \cite{Dunnett1955} providing both adjusted p-values and simultaneous confidence intervals for differences to the control.…

Methodology · Statistics 2023-03-17 Ludwig A. Hothorn , Mario Hasler

Adaptive experiments such as multi-armed bandits offer efficiency gains over traditional randomized experiments but pose two major challenges: invalid inference on the Average Treatment Effect (ATE) due to adaptive sampling and low…

Methodology · Statistics 2026-02-16 Daniel Molitor , Samantha Gold

The use of information from real world to assess the effectiveness of medical products is becoming increasingly popular and more acceptable by regulatory agencies. According to a strategic real-world evidence framework published by U.S.…

Methodology · Statistics 2022-03-22 Jianghao Li , Yu Du , Huayu Liu , Yanyao Yi